A System of Cytokines Encapsulated in ExtraCellular Vesicles

TLDR

Cytokines mediate cell–cell communication, and a newly discovered system uses extracellular vesicles (EVs) to transmit signals. The study aims to decipher the regulatory mechanisms of EV‑encapsulation to better understand cell–cell communication in health and disease. The authors show that many cytokines are released in EV‑encapsulated forms that can trigger biological effects, that EV association depends on the biological system rather than specific cytokines, and that such encapsulated cytokines evade detection by standard assays.

Abstract

Abstract Cytokines are soluble factors that mediate cell–cell communications in multicellular organisms. Recently, another system of cell–cell communication was discovered, which is mediated by extracellular vesicles (EVs). Here, we demonstrate that these two systems are not strictly separated, as many cytokines in vitro , ex vivo , and in vivo are released in EV-encapsulated forms and are capable of eliciting biological effects upon contact with sensitive cells. Association with EVs is not necessarily a property of a particular cytokine but rather of a biological system and can be changed upon system activation. EV-encapsulated cytokines were not detected by standard cytokine assays. Deciphering the regulatory mechanisms of EV-encapsulation will lead to a better understanding of cell–cell communications in health and disease.